Renal Cell Arrest and Damage Biomarkers in Progression and Outcome of Septic AKI

Role of Renal Cell Arrest and Damage Biomarkers in Progression and Outcome of Sepsis Associated AKI

The aim of the current study is to assess the predictive value of renal cell arrest biomarkers (urinary TIMP2 and IGFBP7), renal damage biomarkers (urinary KIM-1) and microscopic examination of urinary sediment in progression and outcome of sepsis associated AKI.

Study Overview

• Status: Completed
• Conditions: AKI - Acute Kidney Injury
• Intervention / Treatment: Diagnostic test: renal cell arrest and damage biomarkers assessment

Detailed Description

Acute kidney injury occurred in about 45-53% of patients with sepsis, and most septic AKI was mild or moderate AKI (KDIGO stage 1 or stage 2).

However, previous study showed that up to 40% of these mild or moderate AKI would progress to more severe AKI (KDIGO stage 3), of which 30% required dialysis and the risk of death increased by 3-fold, as high as 70%. Therefore, early identifying patients at high risk for progressive AKI might help clinicians to enhance individualized monitoring and personalized management in patient with septic AKI, which might prevent or halt the ongoing renal injury and improve the outcome of patients with sepsis.

• Study Type: Interventional
• Enrollment (Actual): 80
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Egypt
  • Alexandria, Egypt, 21526
    • Faculty of Medicine, Aexandria University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• AKI stage 1 or 2 according to KDIGO definition.
• Sepsis is defined based on the third international consensus definitions for sepsis and septic shock (Sepsis-3) as life threatening organ dysfunction caused by a dysregulated host response to infection. At least two of systemic inflammatory response syndrome (SIRS) criteria should be present

Exclusion Criteria:

• Age less than 18 years.
• Patients with pre-existing chronic kidney disease (eGFR<60 ml/min/1.73m2).
• Previous renal replacement therapy.
• Acute kidney injury caused by permanent postrenal obstruction.
• Pregnancy.
• Hepatorenal syndrome.
• Renal transplant recipients.
• Patients for whom survival to 30 days is unlikely due to end stage disease (end stage liver or heart disease or untreatable malignancy).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: septic AKI patients; 80 patients with sepsis associated AKI stage 1 or 2 according to KDIGO definition	Diagnostic test: renal cell arrest and damage biomarkers assessment; measurement of TIMP2 and IGFBP7, KIM-1

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Urinary TIMP2 and IGFBP7 estimation	both will be measured by the ELISA technique	90 days
Urinary KIM-1 estimation	will be measured by the ELISA technique	90 days
Examination of urine sediment	by calculating Perazella score	7 days
progression of AKI	by assessing change in eGFR	90 days
Examination of urine sediment	by calculating Chawla score	7 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
need for renal replacement therapy	need of any dialysis modality	90 days
mortality	death	90 days
length of ICU and hospital stay	duration of stay	90 days

Collaborators and Investigators

• Sponsor: Alexandria University
• Investigators: Study Chair: Mohamed Mamdouh Elsayed, MD, lecturer; Study Chair: Hala S ElWakil, MD, Professor; Principal Investigator: salah s naga, MD, Professor; Study Chair: Mona m tahoun, MD, lecturer; Study Chair: ahmed E El-deeb, Master, Assistant Lecturer

Publications and helpful links

General Publications

• Gunnerson KJ, Shaw AD, Chawla LS, Bihorac A, Al-Khafaji A, Kashani K, Lissauer M, Shi J, Walker MG, Kellum JA; Sapphire Topaz investigators. TIMP2*IGFBP7 biomarker panel accurately predicts acute kidney injury in high-risk surgical patients. J Trauma Acute Care Surg. 2016 Feb;80(2):243-9. doi: 10.1097/TA.0000000000000912.
• Gordon AC, Mason AJ, Thirunavukkarasu N, Perkins GD, Cecconi M, Cepkova M, Pogson DG, Aya HD, Anjum A, Frazier GJ, Santhakumaran S, Ashby D, Brett SJ; VANISH Investigators. Effect of Early Vasopressin vs Norepinephrine on Kidney Failure in Patients With Septic Shock: The VANISH Randomized Clinical Trial. JAMA. 2016 Aug 2;316(5):509-18. doi: 10.1001/jama.2016.10485.
• Maizel J, Daubin D, Vong LV, Titeca-Beauport D, Wetzstein M, Kontar L, Slama M, Klouche K, Vinsonneau C. Urinary TIMP2 and IGFBP7 Identifies High Risk Patients of Short-Term Progression from Mild and Moderate to Severe Acute Kidney Injury during Septic Shock: A Prospective Cohort Study. Dis Markers. 2019 Apr 1;2019:3471215. doi: 10.1155/2019/3471215. eCollection 2019.

Study record dates

Study Major Dates

• Study Start (Actual): October 1, 2023
• Primary Completion (Actual): April 1, 2024
• Study Completion (Actual): June 1, 2024

Study Registration Dates

• First Submitted: September 21, 2023
• First Submitted That Met QC Criteria: September 26, 2023
• First Posted (Actual): October 3, 2023

Study Record Updates

• Last Update Posted (Actual): June 18, 2024
• Last Update Submitted That Met QC Criteria: June 15, 2024
• Last Verified: June 1, 2024

More Information

Terms related to this study

• Keywords: sepsis; AKI; markers; urine sediment
• Additional Relevant MeSH Terms: Kidney Diseases; Urologic Diseases; Renal Insufficiency; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Acute Kidney Injury
• Other Study ID Numbers: markers of septic AKI

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No